Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is a medical emergency that occurs when the contents of tumor cells are released into the bloodstream, either spontaneously or in response to therapy.

TLS usually occurs as an interaction between a proliferative malignancy, high tumor burden, and highly effective therapy. TLS is primarily associated with aggressive lymphomas and leukemias (e.g., Burkitt lymphoma), acute lymphocytic leukemia, acute myeloid leukemia, and chronic myeloid leukemia blast crisis. Although rare, TLS can also be seen with aggressive solid tumors, especially those with highly effective therapies.

Risk Factors

• renal dysfunction

• hyperuricemia

• high tumor burden and/or growth rate

• sensitivity of the malignancy to therapy (either chemotherapy or targeted therapies)

• hypovolemia

• hypotension

• acidic urine

• elevated lactate dehydrogenase at baseline
  

The following table provides more information on risk factors:

(Source: The Tumor Lysis Syndrome. N Engl J Med 2011.)

Diagnosis

Patients can be diagnosed with laboratory TLS or clinical TLS.

The diagnosis of laboratory TLS has classically been based on the Cairo–Bishop criteria which requires two or more of the following abnormalities:

• hyperuricemia (>8 mg/dL)

• hyperkalemia (>6 mmol/L)

• hyperphosphatemia (>4.5 mg/dL)

• hypocalcemia (<7 mg/dL)

A clinical TLS diagnosis also requires one of the following:

• acute renal failure

• cardiac arrhythmia

• seizure

Although lactate dehydrogenase is not included in the clinical or laboratory criteria for diagnosis, it is a useful laboratory marker of tumor proliferation and cell turnover that can be monitored over the course of a patient’s illness.

(Source: The Tumor Lysis Syndrome. N Engl J Med 2011.)

Prevention and Pretreatment

Prophylaxis is important for patients identified at high risk for the development of TLS:

• Administer intravenous (IV) normal saline (2500–3000 ml/m² to achieve urine output of 2 mL/kg/hr; often sufficient for mild TLS).

• If hyperuricemia is present, an agent to reduce uric acid may be required (either allopurinol or rasburicase).

  • Although rasburicase has been shown to be more effective (and preferred in the presence of renal injury), it is very expensive and can be associated with hypersensitivity reactions and hemolytic crisis in the setting of G6PD deficiency.

  • Although institutional practices vary considerably, rasburicase can be considered as a prophylactic measure if baseline uric acid is >8 mg/dL and patients are at high risk for TLS.

  • When measuring uric acid in patients receiving rasburicase, the blood sample should be chilled and processed rapidly to avoid a falsely low uric acid measurement (and thus missing ongoing TLS) due to continued breakdown of uric acid by rasburicase in the blood tube. Allopurinol should be started after normalization of uric acid.

• Diuretics may be necessary to maintain urine output and prevent volume overload.
  

Treatment for Established TLS

• consider intensive care unit (ICU) transfer, depending on clinical status and degree of metabolic derangement (Note: TLS implies a highly responsive tumor and initial response to therapy.)

• lab tests every 4 to 6 hours and treatment of electrolyte abnormalities

• cardiac telemetry monitoring

• intravenous fluids and aggressive treatment of electrolyte abnormalities, in particular hyperkalemia and hyperphosphatemia

• rasburicase for significant hyperuricemia, particularly if renal dysfunction is a concern

• dialysis as a last resort

The following flowchart is helpful for the initial assessment and management of TLS:

(Source: The Tumor Lysis Syndrome. N Engl J Med 2011.)